Oncostatin M orchestrates collective epithelial migration via HIF1A activation
- 1Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR USA
- 2Capsida Biotherapeutics Inc., Thousand Oaks, CA USA
- 3Knight Cancer Institute, Oregon Health and Science University, Portland, OR USA
Abstract
Extracellular signals strongly influence cell behavior, yet the mechanisms by which specific ligands mediate changes in phenotype remain unclear. The cytokine Oncostatin M (OSM) regulates homeostasis, wound healing, inflammation, and cancer progression. We previously found that OSM induces collective cell migration (CCM), a process whereby cells move as cohesive units while retaining cell-cell contacts, in MCF10A mammary epithelial cells. Here, we investigated how OSM drives CCM by comparing its effects with those elicited by epidermal growth factor (EGF) and interferon gamma (IFNG), defining ligand-specific phenotypes and molecular networks. Integrative transcriptomic and proteomic analyses identified hypoxia-inducible factor-1 (HIF1A) and signal transducer and activator of transcription 3 (STAT3) as central regulators of OSM responses. Functional validation revealed that HIF1A drives transcriptional programs associated with hypoxia, metabolic reprogramming, and immune pathways. Complement signaling emerged as a downstream effector of HIF1A, and its inhibition disrupted OSM-induced clustering and CCM. These findings establish a mechanistic link between OSM signaling, HIF1A activation, and CCM, demonstrating how cytokine-driven transcriptional reprogramming coordinates epithelial cell migration. Analysis of public breast cancer data indicate that this pathway is active in human tumors and may contribute to tissue remodeling, repair, and metastasis.
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BibTeX
@article{mclean2026oncostatin,
title = {{Oncostatin M orchestrates collective epithelial migration via HIF1A activation}},
author = {Ian C. McLean and Sean M. Gross and Tiera A. Liby and Mark A. Dane and Daniel S. Derrick and Laura M. Heiser},
journal = {NPJ Systems Biology and Applications},
year = {2026},
month = jul,
doi = {10.1038/s41540-026-00778-0},
url = {https://doi.org/10.1038/s41540-026-00778-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Oncostatin M orchestrates collective epithelial migration via HIF1A activation
AU - Ian C. McLean
AU - Sean M. Gross
AU - Tiera A. Liby
AU - Mark A. Dane
AU - Daniel S. Derrick
AU - Laura M. Heiser
PY - 2026
DA - 2026/07/06
JO - NPJ Systems Biology and Applications
DO - 10.1038/s41540-026-00778-0
UR - https://doi.org/10.1038/s41540-026-00778-0
AB - Extracellular signals strongly influence cell behavior, yet the mechanisms by which specific ligands mediate changes in phenotype remain unclear. The cytokine Oncostatin M (OSM) regulates homeostasis, wound healing, inflammation, and cancer progression. We previously found that OSM induces collective cell migration (CCM), a process whereby cells move as cohesive units while retaining cell-cell contacts, in MCF10A mammary epithelial cells. Here, we investigated how OSM drives CCM by comparing its effects with those elicited by epidermal growth factor (EGF) and interferon gamma (IFNG), defining ligand-specific phenotypes and molecular networks. Integrative transcriptomic and proteomic analyses identified hypoxia-inducible factor-1 (HIF1A) and signal transducer and activator of transcription 3 (STAT3) as central regulators of OSM responses. Functional validation revealed that HIF1A drives transcriptional programs associated with hypoxia, metabolic reprogramming, and immune pathways. Complement signaling emerged as a downstream effector of HIF1A, and its inhibition disrupted OSM-induced clustering and CCM. These findings establish a mechanistic link between OSM signaling, HIF1A activation, and CCM, demonstrating how cytokine-driven transcriptional reprogramming coordinates epithelial cell migration. Analysis of public breast cancer data indicate that this pathway is active in human tumors and may contribute to tissue remodeling, repair, and metastasis.
SN - 2056-7189
ER -